The proposed research project concerns the different mechanisms by which digitalis induces cardiac arrhythmias. The tissues to be studied included the sinus node, ventricular Purkinje fibers and ventricular muscle fibers. The techniques involved include a measurement of membrane potential, current and contractility. The problems to be $ investigated include the following topics: the effects of different calcium levels on the contractility and action potential configuration of cardiac tissues in the presence and in the absence of strophanthidin; the effect of different rates of discharge on the relationship between calcium and strophanthidin; the effect of different calcium concentrations on the action of strophanthidin in quiescent fibers; the effect of substances known to increase intracellular calcium concentration on strophanthidin toxicity; the action of some therapeutic agents on digitalis toxicity; the effect of strophanthidin on some of the currents responsible for automatic discharge; the effect of different doses of strophanthidin on potassium movements. The results of these procedures should provide useful information on the mechanisms by which digitalis induces arrhythmias. In addition, information should be obtained on the mechanism by which some agents favor and other antagonize the cardiac arrhythmias induced by digitalis.